目的探讨肝豆状核变性、乙型肝炎不同肝功能状态时血浆铜蓝蛋白水平的差异及其临床意义。方法用终末期肝病模型(model for end-stage liver disease,MELD)评分衡量肝功能损害的严重性,采用散射比浊法检测并比较分析肝豆状核变性、慢加...目的探讨肝豆状核变性、乙型肝炎不同肝功能状态时血浆铜蓝蛋白水平的差异及其临床意义。方法用终末期肝病模型(model for end-stage liver disease,MELD)评分衡量肝功能损害的严重性,采用散射比浊法检测并比较分析肝豆状核变性、慢加急性肝衰竭极期以及恢复期、慢性乙型肝炎患者的血浆铜蓝蛋白水平。结果肝豆状核变性(n=50)、慢加急性肝衰竭极期和恢复期(n=30)、慢性乙型病毒性肝炎患者(n=50)的MELD评分分别为11.1±6.5、20.4±4.2、10.9±4.9、9.6±9.8,血浆铜蓝蛋白分别为(0.065±0.036)g/L、(0.176±0.037)g/L、(0.210±0.056)g/L、(0.197±0.038)g/L;血浆铜蓝蛋白水平4组之间的两两比较存在差异(F=111.4,P<0.001),肝豆状核变性患者低于其他3组(P<0.001)。结论肝豆状核变性血浆铜蓝蛋白水平显著降低。相对于肝豆状核变性,没有肝衰竭的慢性乙型肝炎血浆铜蓝蛋白水平几乎正常。慢加急性肝衰竭极期血浆铜蓝蛋白水平仅轻度下降,随着肝功能衰竭的恢复,血浆铜蓝蛋白恢复正常。展开更多
Background: Transcranial ultrasound may be used to detect increased iron leve ls of the substantia nigra (SN) in patients with Parkinson disease (PD) and in c ontrol subjects. It is not known whether iron accumulation...Background: Transcranial ultrasound may be used to detect increased iron leve ls of the substantia nigra (SN) in patients with Parkinson disease (PD) and in c ontrol subjects. It is not known whether iron accumulation in PD is a primary or secondary phenomenon. However, sequence variations in genes involved in iron me tabolism have been linked to basal ganglia disorders. One of these is ceruloplas min (Cp), which is vitally involved in iron transport across the cell membrane. Methods: One hundred seventy-six patients with PD according to the UK Brain Ba nk criteria and 180 ethnically matched control subjects, who were previously exa mined for SN iron signal changes by transcranial ultrasound, were examined for m utations in the Cp gene using denaturing high-performance liquid chromatograph y and subsequent sequencing for verification of unequivocal signals. Immunohisto chemistry of PD midbrains was performed to examine the presence of Cp in Lewy bo dies. Results: Five novel missense variations were detected. One of these (I63T) was found in a single PD patient. A known variation (D554E)was significantly as sociated with PD and the ultrasound marker for increased SN iron levels. Moreove r, a third sequence variation (R793H) was found to segregate with the ultrasound marker for increased iron levels in patients an d control subjects. Immunohistochemistry demonstrated that Cp co-localizes wit h Lewy bodies in PD. Conclusions: Detection of sequence variations in a single P arkinson disease (PD) patient or associated with the ultrasound marker for incre ased substantia nigra iron levels and the presence of ceruloplasmin (Cp) immunor eactivity in Lewy bodies underline a suspected role for Cp in the pathogenesis o f PD. Further functional analyses are warranted to investigate whether these var iations are causally linked to the complex pathogenesis of PD in a subset of cas es.展开更多
文摘目的探讨肝豆状核变性、乙型肝炎不同肝功能状态时血浆铜蓝蛋白水平的差异及其临床意义。方法用终末期肝病模型(model for end-stage liver disease,MELD)评分衡量肝功能损害的严重性,采用散射比浊法检测并比较分析肝豆状核变性、慢加急性肝衰竭极期以及恢复期、慢性乙型肝炎患者的血浆铜蓝蛋白水平。结果肝豆状核变性(n=50)、慢加急性肝衰竭极期和恢复期(n=30)、慢性乙型病毒性肝炎患者(n=50)的MELD评分分别为11.1±6.5、20.4±4.2、10.9±4.9、9.6±9.8,血浆铜蓝蛋白分别为(0.065±0.036)g/L、(0.176±0.037)g/L、(0.210±0.056)g/L、(0.197±0.038)g/L;血浆铜蓝蛋白水平4组之间的两两比较存在差异(F=111.4,P<0.001),肝豆状核变性患者低于其他3组(P<0.001)。结论肝豆状核变性血浆铜蓝蛋白水平显著降低。相对于肝豆状核变性,没有肝衰竭的慢性乙型肝炎血浆铜蓝蛋白水平几乎正常。慢加急性肝衰竭极期血浆铜蓝蛋白水平仅轻度下降,随着肝功能衰竭的恢复,血浆铜蓝蛋白恢复正常。
文摘Background: Transcranial ultrasound may be used to detect increased iron leve ls of the substantia nigra (SN) in patients with Parkinson disease (PD) and in c ontrol subjects. It is not known whether iron accumulation in PD is a primary or secondary phenomenon. However, sequence variations in genes involved in iron me tabolism have been linked to basal ganglia disorders. One of these is ceruloplas min (Cp), which is vitally involved in iron transport across the cell membrane. Methods: One hundred seventy-six patients with PD according to the UK Brain Ba nk criteria and 180 ethnically matched control subjects, who were previously exa mined for SN iron signal changes by transcranial ultrasound, were examined for m utations in the Cp gene using denaturing high-performance liquid chromatograph y and subsequent sequencing for verification of unequivocal signals. Immunohisto chemistry of PD midbrains was performed to examine the presence of Cp in Lewy bo dies. Results: Five novel missense variations were detected. One of these (I63T) was found in a single PD patient. A known variation (D554E)was significantly as sociated with PD and the ultrasound marker for increased SN iron levels. Moreove r, a third sequence variation (R793H) was found to segregate with the ultrasound marker for increased iron levels in patients an d control subjects. Immunohistochemistry demonstrated that Cp co-localizes wit h Lewy bodies in PD. Conclusions: Detection of sequence variations in a single P arkinson disease (PD) patient or associated with the ultrasound marker for incre ased substantia nigra iron levels and the presence of ceruloplasmin (Cp) immunor eactivity in Lewy bodies underline a suspected role for Cp in the pathogenesis o f PD. Further functional analyses are warranted to investigate whether these var iations are causally linked to the complex pathogenesis of PD in a subset of cas es.
